Mini-Review: Computational Structure-Based Design of Inhibitors that Target Protein Surfaces
Author: Zeng J.
Source: Combinatorial Chemistry & High Throughput Screening, Volume 3, Number 5, October 2000 , pp. 355-362(8)
Publisher: Bentham Science Publishers
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Abstract:
Finding drugs that inhibit protein-protein interactions is usually difficult. While computer-aided design is used widely to facilitate the drug discovery process for protein targets with well-defined binding pockets, its application to the design of inhibitors targeting a protein surface is very limited. In this mini-review we address two aspects of this issue: firstly, we overview the current state of design methodology for inhibitors specifically targeting protein surfaces, and secondly, we briefly outline recent advances in computational methods for structure-based drug design. These methods are closely related to protein docking and protein recognition, the difference being that in ligand design, ligands are built on a fragment-by-fragment basis. A novel scheme of computational combinatorial ligand design developed for the design of inhibitors that interfere with protein-protein interaction is described in detail. Current applications and limitations of this methodology, as well as its future prospects, are discussed.
Keywords: Protein Surfaces; Inhibit protein-protein interactions; Computer aided design; Computational methods; Structure-based drug design; Computational combinatorial ligand design; Inhibitor design; Erythropoietin (EPO); Thromobopoietin (TPO); EPO-peptide complex; SH3 Inhibitors; Immunoglobulin Inhibitors; Computational Combinatorial Inhibitor Design
Language: English
Document Type: Review article
DOI: 10.2174/1386207003331490
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